The ongoing focus of the laboratory is to understand in detail the structure/function relationships of cell surface molecules involved in the immune response. In particular, we have made significant progress over the past year in several areas: A. exploting molecular genetic techniques to generate a panel of cell lines expressing soluble counterparts of the murine class I major histocompatibility antigens H-2Kb, H-2Dd, H-2Ld, and H-2Kk; as well as the H-2Kb mutant H-2Kbm10; B. using the purified soluble molecules from H-2Dd and H-2Kb to attempt to grow crystals for X-ray crystallography; C. using the purified soluble molecules to study the biochemical and functional behavior of the H-2Dd molecule; D. analysis of the expression and function of in vitro lariat branch point mutations expected to control the choice of splice acceptor sites for the eighth exon of H-2Kb and H-2Dd; E. testing hypotheses about tolerance and T cell education by generating transgenic mice that express the soluble counterpart of the H-2Dd and H-2Kb genes.